Combinative improving effect of increased solubility and the use of absorption enhancers on the rectal absorption of uracil in beagle dogs.
An improvement of the rectal absorption of uracil was examined by the application of absorption enhancers in addition to the increased solubility of uracil. Uracil was ground with additives such as MgO, sodium 2,6-dihydroxybenzoate, human serum albumin or hydroxypropylmethylcellulose acetate succinate. Aqueous, oily and powdery formulations, which consisted of the ground mixtures, nicotinamide, urea and absorption enhancers such as polyoxyethylene (23) cetylether (BC-23) or sodium caprate, were prepared. Uracil solubility in the aqueous formulations was increased about 4-13 times that in the corresponding control formulations. When rectally administered to beagle dogs, marked increases in the plasma uracil level were observed in some of the cases of aqueous and oily formulations. In the powdery formulations and formulations containing macromolecular additives, however, absorption improvements was not observed. The results indicated that an improvement in the absorption of uracil was caused by the combinative improving effect of the increased uracil solubility and the promoting effect of absorption enhancers.
Takeichi
Y
Y
Pharmaceutical Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Baba
K
K
Kinouchi
Y
Y
Iida
Y
Y
Umeno
Y
Y
Muranishi
S
S
Nakai
Y
Y
D000042:Absorption / Q000187:drug effects; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004357:Drug Synergism; D006801:Humans; D008297:Male; D012007:Rectum / Q000378:metabolism*; D012996:Solutions; D014498:Uracil / Q000493:pharmacokinetics*
D012996:Solutions; D014498:Uracil